Differential susceptibility of human alcohol dehydrogenase isoenzymes to anions

Human liver alcohol dehydrogenase (ADH) isoenzymes beta 1 beta 1, gamma 1 gamma 1 from Caucasian individuals with 'typical' ADH and beta 2 beta 2-Bern from Caucasian individuals with 'atypical' phenotype differed in their susceptibility to anions. At pH 7.0 beta 1 beta 1 and gamma 1 gamma 1 were more active in Tris-HCl buffer than in sodium phosphate buffer but less active in Hepes-NaOH and Mops-NaOH. beta 2 beta 2-Bern showed the same activity in all these buffers. At pH 7.0 and at low concentrations (50-100 mM) chloride activated the ethanol oxidation by beta 1 beta 1 and gamma 1 gamma 1, whereas sulfate showed no effect. At anion concentrations above 100 mM all isoenzymes were inhibited. At pH 10.5 beta 1 beta 1 and gamma 1 gamma 1 were not activated. Measuring the acetaldehyde reduction, no comparable activation by chloride was observed; all three isoenzymes were inhibited, at significantly lower anion concentrations. These anion effects can be correlated with the different primary structures of the isoenzymes around the active site and the coenzyme binding site.